1-Hydroxybenzotriazole → N-[(1S,2S,4R)-1-Benzyl-4-(3,3-dimethylbutylcarbamoyl)-2-hydroxypentyl]-3-methanesulfonyl-benzamide

HRID 1373109ノート

反応式

HRID 1373109 の反応式
ON1C2C=CC=CC=2N=N1.ClCCl.CN(C=O)C.[CH3:19][S:20]([C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=1)[C:26]([OH:28])=O)(=[O:22])=[O:21].[CH3:32][C:33]([CH3:54])([CH3:53])[CH2:34][CH2:35][NH:36][C:37](=[O:52])[C@H:38]([CH3:51])[CH2:39][C@H:40]([OH:50])[C@@H:41]([NH2:49])[CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>CN(C=O)C.ClCCl>[CH2:42]([C@H:41]([NH:49][C:26](=[O:28])[C:25]1[CH:29]=[CH:30][CH:31]=[C:23]([S:20]([CH3:19])(=[O:21])=[O:22])[CH:24]=1)[C@@H:40]([OH:50])[CH2:39][C@H:38]([C:37](=[O:52])[NH:36][CH2:35][CH2:34][C:33]([CH3:32])([CH3:53])[CH3:54])[CH3:51])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

参加物

7

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 2203803-Methanesulfonylbenzoic acidHCID 22350042dichloromethane N,N-dimethylformamideHCID 68890142(2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenylhexanoic acid (3,3-dimethylbutyl)-amide

生成物 1

HCID 58780868N-[(1S,2S,4R)-1-Benzyl-4-(3,3-dimethylbutylcarbamoyl)-2-hydroxypentyl]-3-methanesulfonyl-benzamide収率 49%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒3 回

実験手順

N-Cyclohexylcarbodiimide-N′-methyl polystyrene (100 mg @ 1.70 mmol/g; ex. Novabiochem) was treated with dichloromethane (0.5 ml) followed by a solution of 1-hydroxybenzotriazole (22 mg, 0.14 mmol) in 4:1 dichloromethane/DMF (0.5 ml). 3-Methanesulfonyl benzoic acid (28 mg, 0.14 mmol) in DMF (0.5 ml) and (2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenylhexanoic acid (3,3-dimethylbutyl)-amide (D2) (30 mg, 0.094 mmol) in dichloromethane (0.5 ml) were then added and the mixture was stirred gently overnight at room temperature. It was then diluted with dichloromethane (0.5 ml) and treated with methylisocyanate polystyrene (100 mg @ 1.80 mmol/g; ex. Novabiochem) and tris-(2-aminoethyl)-amine polystyrene (100 mg @ 3.20 mmol/g; ex. Novabiochem), and the mixture was stirred gently for a further 1.5 h. It was then filtered and the spent resins were washed with DMF (1 ml) and dichloromethane (1 ml). The combined filtrates were evaporated to dryness and the residue was triturated with diethyl ether/hexane to afford the title compound (E1) as a white solid (23 mg, 49%).

後処理

  1. stirringthe mixture was stirred gently for a further 1.5 h
  2. filtrationIt was then filtered
  3. washthe spent resins were washed with DMF (1 ml) and dichloromethane (1 ml)
  4. customThe combined filtrates were evaporated to dryness
  5. customthe residue was triturated with diethyl ether/hexane

出典と根拠

ORDレコード
ord-87dec13e40ca4ffaaad39c6dfecd0c64
出典データセット
uspto-grants-2007_01
特許番号
US07160905B2

反応ノート

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